Response to erenumab assessed by HIT-6 is modulated by genetic factors and arterial hypertension - an explorative cohort study.

Zecca, Chiara; Terrazzino, Salvatore; Para, Davide; Campagna, Giovanna; Viana, Michele; Schankin, Christoph J; Gobbi, Claudio (2023). Response to erenumab assessed by HIT-6 is modulated by genetic factors and arterial hypertension - an explorative cohort study. European journal of neurology, 30(4), pp. 1099-1108. Wiley 10.1111/ene.15678

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BACKGROUND

Response predictors to erenumab (ERE) in migraine patients would benefit their clinical management. We investigate associations between patients' clinic characteristics and polymorphisms at CALCRL and RAMP1 genes and response to ERE treatment measured as clinically meaningful improvement of the headache impact test 6 (HIT-6) score.

METHODS

Post-hoc analysis of a prospective, multicenter, investigator-initiated study involving 110 migraine patients starting ERE 70 mg/month. Demographics, medical history, and migraine-related burden measured by HIT-6 score were collected during 3 months before and after ERE start. Selected polymorphic variants of calcitonin receptor-like receptor and receptor activity-modifying protein-1 genes were determined using Real-time PCR. Logistic regression models identified independent predictors for response to ERE, defined as HIT-6 score improvement ≥8 points (HIT-6 responders [HIT-6RESP], vs. HIT-6 non-responders [HIT-6NRESP]).

RESULTS

At month 3, 58 (52.7%) patients were HIT-6RESP. Comorbid hypertension predicted a lower probability of being HIT-6RESP [OR (95%CI] 0.160 (0.047-0.548), p=0.003). Compared to major alleles, minor alleles CALCRL rs6710852G and RAMP rs6431564G conferred an increased probability of being HIT-6RESP [for each G allele: OR (95%CI): 2.82(1.03-7.73), p=0.043; OR 95%CI): 2.10(1.05-4.22), p=0.037]. RAMP1 rs13386048A and RAMP1 rs12465864G decreased this probability [for each rs13386048A, OR (95%CI): 0.53(0.28-0.98), p=0.042; for each rs12465864G, OR(95%CI): 0.32(0.13-0.75), p=0.009). A genetic risk score based on the presence and number of identified risk alleles resulted independently associated with HIT-6RESP (OR, 0.49; 95%CI, 0.33-0.72; p= 0.0003) surviving Bonferroni's correction.

CONCLUSIONS

Response to ERE was associated with comorbid hypertension and specific allelic variants at CALCRL and RAMP1 genes. Results require confirmation in future studies.

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